ArticleThe Journal of clinical investigation2004
Enhanced neuronal excitability in the absence of neurodegeneration induces cerebellar ataxia.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00202397 (Phase 2 Study of Riluzole Effects on Patients With Chronic Cerebellar Ataxia), which is not on this map. Cited by 65 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase 2 Study of Riluzole Effects on Patients With Chronic Cerebellar Ataxia
Who cites it
65 citing papers in PubMed, 112 citations in OpenAlex.
- Proteomic profiling of ANO10-deficient SH-SY5Y cells reveals candidate pathways relevant to SCAR10.Scientific reports · 2026Article
- Purkinje cell intrinsic activity shapes cerebellar development and function.Nature communications · 2026Article
- SCA27B: a treatable ataxia-from falls to independence.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- Molecular hallmarks of neurodegeneration in polyglutamine spinocerebellar ataxias.Cell death & disease · 2025Review
- Glutamatergic Neurons in the Cerebellar Lateral Nucleus Contribute to Motor Deficits Induced by Chronic Sleep Disturbance.Brain sciences · 2025Article
- Long-Term Follow-Up before and during Riluzole Treatment in Six Patients from Two Families with Spinocerebellar Ataxia Type 7.Cerebellum (London, England) · 2024Article
- Targeting Ion Channels and Purkinje Neuron Intrinsic Membrane Excitability as a Therapeutic Strategy for Cerebellar Ataxia.Life (Basel, Switzerland) · 2023Review
- ANO10 Function in Health and Disease.Cerebellum (London, England) · 2023Review
- Article
- Viewpoint: spinocerebellar ataxias as diseases of Purkinje cell dysfunction rather than Purkinje cell loss.Frontiers in molecular neuroscience · 2023Review
- KCurrent neuropharmacology · 2023Review
- Acute Cerebellar Inflammation and Related Ataxia: Mechanisms and Pathophysiology.Brain sciences · 2022Review
- Current and emerging treatment modalities for spinocerebellar ataxias.Expert review of neurotherapeutics · 2022Review
- Vulnerability of Human Cerebellar Neurons to Degeneration in Ataxia-Causing Channelopathies.Frontiers in systems neuroscience · 2022Review
- Physiology and Therapeutic Potential of SK, H, and M Medium AfterHyperPolarization Ion Channels.Frontiers in molecular neuroscience · 2021Review
- Pathogenic mechanisms underlying spinocerebellar ataxia type 1.Cellular and molecular life sciences : CMLS · 2020Review
- Pharmacology of Small- and Intermediate-Conductance Calcium-Activated Potassium Channels.Annual review of pharmacology and toxicology · 2020Review
- Disrupted Calcium Signaling in Animal Models of Human Spinocerebellar Ataxia (SCA).International journal of molecular sciences · 2019Review
- Integrative network and brain expression analysis reveals mechanistic modules in ataxia.Journal of medical genetics · 2019Article
- Ion channel dysfunction in cerebellar ataxia.Neuroscience letters · 2019Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cerebellar ataxia, a devastating neurological disease, may be initiated by hyperexcitability of deep cerebellar nuclei (DCN) secondary to loss of inhibitory input from Purkinje neurons that frequently degenerate in this disease. This mechanism predicts that intrinsic DCN hyperexcitability would cause ataxia in the absence of upstream Purkinje degeneration. We report the generation of a transgenic (Tg) model that supports this mechanism of disease initiation. Small-conductance calcium-activated potassium (SK) channels, regulators of firing frequency, were silenced in the CNS of Tg mice with the dominant-inhibitory construct SK3-1B-GFP. Transgene expression was restricted to the DCN within the cerebellum and was detectable beginning on postnatal day 10, concomitant with the onset of cerebellar ataxia. Neurodegeneration was not evident up to the sixth month of age. Recordings from Tg DCN neurons revealed loss of the apamin-sensitive after-hyperpolarization current (IAHP) and increased spontaneous firing through SK channel suppression, indicative of DCN hyperexcitability. Spike duration and other electrogenic conductance were unaffected. Thus, a purely electrical alteration is sufficient to cause cerebellar ataxia, and SK openers such as the neuroprotective agent riluzole may reduce neuronal hyperexcitability and have therapeutic value. This dominant-inhibitory strategy may help define the in vivo role of SK channels in other neuronal pathways.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.